Chloride → 2-(4-Chloro-phenyl)-4-(2-methoxy-ethyl)-thiazole-5-carboxylic acid methyl ester

HRID 601497Notes

Reaction equation

HRID 601497 reaction equation
[Cl-].[CH3:2][O:3][C:4](=[O:12])[CH2:5][C:6](=O)[CH2:7][CH2:8][O:9][CH3:10].[Cl:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([NH2:20])=[S:19])=[CH:16][CH:15]=1.CO>ClCCl>[CH3:2][O:3][C:4]([C:5]1[S:19][C:18]([C:17]2[CH:21]=[CH:22][C:14]([Cl:13])=[CH:15][CH:16]=2)=[N:20][C:6]=1[CH2:7][CH2:8][O:9][CH3:10])=[O:12]

Participants

6

Reactant 4

HCID 312ChlorideHCID 887MethanolHCID 542416Methyl 5-methoxy-3-oxopentanoateHCID 27348264-Chlorothiobenzamide

Product 1

HCID 575016962-(4-Chloro-phenyl)-4-(2-methoxy-ethyl)-thiazole-5-carboxylic acid methyl esterYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Add a 1.0 M solution of sufuryl chloride in dichloromethane (20.0 mL, 20.0 mmol) dropwise to a solution of 5-methoxy-3-oxo-pentanoic acid methyl ester (3.0 g, 18.8 mmol) in dichloromethane (20.0 mL) at 0° C. and stir under nitrogen at 0° C. for 2 h. Concentrate the reaction mixture on a rotavap (rotary evaporator), keeping the bath temperature at RT. Add 4-chlorothiobenz-amide (3.67 g, 21.5 mmol) to the residue, followed by methanol (30.0 mL) and heat to 60° C. for 18 h. Quench the reaction with water and extract with EtOAc (2×). Combine the organic portions, wash with brine, dry over MgSO4, filter, and concentrate under vacuum. Purify by flash chromatography on silica gel, using a gradient of EtOAc/Hexane (0-60%) to give the title compound (3.3 g, 57%). Exact mass=311.0, MS (ES+) 312.0 (M+1). 1H NMR (CDCl3): δ 7.89 (d, 2H, J=8.8 Hz), 7.40 (d, 2H, J=8.8 Hz), 3.88 (s, 3H), 3.82 (t, 2H, J=6.8 Hz), 3.47 (t, 2H, J=6.8 Hz), 3.38 (s, 3H).

Workup

  1. concentrationConcentrate the reaction mixture on a rotavap
  2. custom(rotary evaporator)
  3. customat RT
  4. temperatureheat to 60° C. for 18 h
  5. customQuench
  6. customthe reaction with water
  7. extractionextract with EtOAc (2×)
  8. washCombine the organic portions, wash with brine
  9. dry with materialdry over MgSO4
  10. filtrationfilter
  11. concentrationconcentrate under vacuum
  12. customPurify by flash chromatography on silica gel

Sources & evidence

ORD record
ord-cc2899adad69440d84c701669525680b
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

Loading…